Exendin-4 effect on pancreatic islet function of donor rats with cardiac death at different heat ischemia time

doi:10.3969/j.issn.2095-4344.2014.36.002

Abstract

Abstract:

BACKGROUND: The use of donor rat of cardiac death inevitably experiences warm ischemia injury, so the length of warm ischemia time plays a significant role on the number and function of pancreatic islet obtained.
OBJECTIVE: To investigate the effect of Exendin-4 on pancreatic islet function of donor rats with cardiac death at different heat ischemia time.
METHODS: Islet cells from Wistar rats were cultured in vitro and randomly divided into three groups according to the experimental conditions: 0, 30, 45 min heat ischemia groups. Each group was further assigned into two subgroups, control group was cultured for 24 hours while experimental group wad cultured with 10 nmol/L Exendin-4 for 24 hours. The number of isolated pancreatic islets was calculated with diphenylthiocarbazone staining, and the purity of the extracted islets was adjusted. The viability of the islets was examined by AO/EB staining, and insulin secretion index assay was used to detect the function of the islets.
RESULTS AND CONCLUSION: With the time of heat ischemia increasing, the number, purity, viability and function of islet cells obtained were decreased. After the cells in heat ischemia 0, 30, 45 min groups were cultured with 10 nmol/L Exendin-4 for 24 hours, the number, purity and viability of isolated and purified islets were increased compared to the group without added Exendin-4. There was significant difference between experimental group and control group in 30-minute and 45-minute ischemia groups (P < 0.05). Exendin-4 can protect pancreatic islet cells in donor rats with cardiac death at different heat ischemia times, reduce the apoptosis, and improve islet survival and functions. The use of Exendin-4 can be an effective pretreatment method at early ischemia phase of islet transplantation.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: islets of langerhans, warm ischemia, islet transplantation

CLC Number:

R318

Che Yan-peng, Liu Yong-feng, Song Wen-qing, Liang Shi-bo . Exendin-4 effect on pancreatic islet function of donor rats with cardiac death at different heat ischemia time[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(36): 5747-5751.

Figures/Tables 2

References

[1] Nathan D. Long-team complication of diabetes mellitus. N Engl J Med.1993;328:1676-1684.
[2] Diabetes Control and Complications Trial Research Group.The effect of intensive treatment of diabetes on the development of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med.1993; 329:977-986.
[3] Bloomgarden ZT.American diabetes Association postgraduate course, 1996: Treatment and prevention of diabetes. Diabetes Care.1996;19:784-786.
[4] Sutherland DE, Gruessner AC, Gruessner RW. Pancreas transplantation: A review. Transplant Proc.1998;30: 1940-1943.
[5] Fioretto P, Steffes MW, Sutherland DR, et al.Reversal of lesions of diabetic nephropathy after pancreas transplantation.N Engl J Med.1998;339(2):69-75.
[6] Tyden G, Bolinder J, Solders G,et al.Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation.Transplantation.1999;67:645-648.
[7] Shapiro AM, Lakey JR, Paty BW, et al. Strategic opportunities in c1inical islet transplantation. Transplantation. 2005;79: 1304-1307.
[8] Shapiro AM, Rieordi C, Hering BJ, et al.Internationa1 tria1 of the Edmonton Protocol for islet transplantation.N Engl J Med. 2006;355:1318-1330.
[9] Wakai A. Effect of adenosine on ischemia-reperfusion injury associated with rat pancreas transplantation. Br J Surg. 2002; 89:494-496.
[10] Li Y, Hansotia T, Yusta B, et al.Glucagon-like-peptide-1 receptor signaling modulates β cell apoptosis. J Biol Chem. 2003;278:471-478.
[11] Farilla L, Bulotta A, Hirshberg B, et al.Glucagon-like-peptide-l inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology.2003;14: 5149-5158.
[12] Frank A,Deng S,Huang X,et al.Transplantation for type 1 diabetes: vascularization whole organ pancreas with isolated pancreatic islets. Ann Surg.2004;240: 631-640.
[13] Shapiro AM, Rieordi C, Hering BJ, et al.Internationa1 tria1 of the Edmonton Protocol for islet transplantation. N Eng J Med. 2006;355:1318-1330.
[14] Johnson PR, white SA, London NJ. Collagenase and human islet isolation. Cell Transplant 1996;5:437-452.
[15] Rosenberg L, wang R, Paraskevas S, et al. Structural and functional changes resulting from islet isolation lead to islet cell death.Surgery 1999;126:393-398.
[16] Bottino R, Balamurugan AN, Bertera S,et al. Preservation of human islet cell functional maee by anti-oxidative action of a novel SOD mimic compound. Diabetes.2002;51: 2561-2667.
[17] De Ore K, Greig NH, Holloway HW, et al.The effects of GLP-1 on insulin release in young and old rats in the fasting state and during an intravenous glucose tolerance test. J Gerontol A Biol Sci Med Sci.1997;52:245-249.
[18] Holst JJ, Gromada J.Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. J Physiol Endocrinol Metab 2004;287(3): 199-206.
[19] Deacon CF. Therapeutic strategies based on glucagon-like peptide 1. Diabetes 2004;53(5):2181-2189.
[20] Hoist JJ.Therapy of type 2 diabetes mellitus based on the action of glucagon-like peptide 1. Diabetes Metab.2002;18(2): 430-441.
[21] Gedulin BR, Nikoulina SE,Smith PA,et al. Exenatide (exendin-4) improves insulin sensitivity and{beta}-cell mass in insulin-resistant Obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology.2005;146: 2069-2076.
[22] Tian L, Gao J, Weng G, et al.Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts. Transpl Int. 2011;24(8):856-864.
[23] Padmasekar M, Lingwal N, Samikannu B, et al. Exendin-4 protects hypoxic islets from oxidative stress and improves islet transplantation outcome.Endocrinology. 2013;154(4): 1424-1433.
[24] Jia X, Sharma A, Kumagai-Braesch M, et al.Exendin-4 increases the expression of hypoxia-inducible factor-1α in rat islets and preserves the endocrine cell volume of both free and macroencapsulated islet grafts. Cell Transplant. 2012; 21(6):1269-1283.
[25] 林玉晶,王琛,洪天配.胰升糖素样肽1及其类似物在胰岛移植中的应用前景[J].中国糖尿病杂志,2010,18(10):728-731.
[26] 李达.Exendin-4对诱导大鼠胰腺导管来源干细胞向胰岛素分泌细胞定向分化的实验研究[J].沈阳:中国医科大学.2011.
[27] Toyoda K, Okitsu T, Yamane S, et al. GLP-1 receptor signaling protects pancreatic beta cells in intraportal islet transplant by inhibiting apoptosis. Biochem Biophys Res Commun.2008; 367(4):793-798.
[28] Bohman S, Waern I, Andersson A,et al.Transient beneficial effects of exendin-4 treatment on the function of microencapsulated mouse pancreatic islets. Cell Transplant. 2007;16(1):15-22.
[29] Sharma A, Sörenby A, Wernerson A, et al. Exendin-4 treatment improves metabolic control after rat islet transplantation to athymic mice with streptozotocin-induced diabetes. Diabetologia. 2006;49(6):1247-1253.
[30] Wu Z, Liu S, Hassink M, et al. Development and evaluation of 18F-TTCO-Cys40-Exendin-4: a PET probe for imaging transplanted islets. J Nucl Med. 2013;54(2):244-251.
[31] Juang JH, Kuo CH, Wu CH, et al.Exendin-4 treatment expands graft beta-cell mass in diabetic mice transplanted with a marginal number of fresh islets. Cell Transplant. 2008;17(6):641-647.
[32] 宋光明,申竹芳.新型糖尿病治疗药物exendin-4的研究进展[J].中国临床药理学杂志,2008,24(2)156-160.
[33] 车彦鹏.Exendin-4对不同热缺血时间心死亡供体大鼠胰岛功能影响的实验研究[D].沈阳:中国医科大学,2011.
[34] Webb M, James RF. Growth restriction and exendin 4 promote endocrine expression in cultured islet cells derived from patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Endocr Res. 2005;31(2):99-109.
[35] King A, Lock J, Xu G, et al. Islet transplantation outcomes in mice are better with fresh islets and exendin-4 treatment. Diabetologia.2005;48(10):2074-2079.
[36] 苗新宇.胰高血糖素样肽-1对胰岛β细胞增殖、凋亡、自噬的影响及机制探讨[D].北京:中国人民解放军军医进修学院:老年内分泌及代谢病,2013.
[37] 班绎娟,许樟荣.胰高血糖素样肽-1类似物治疗2型糖尿病的研究进展[J].中华老年多器官疾病杂志,2014,13(5):391-395.
[38] 刘芳,余江毅.GLP-1对2型糖尿病胰岛细胞及脂肪细胞的作用研究[J].医学研究杂志,2014,43(5):10-12.
[39] 徐艳花.胰腺小分子活性肽对体外培养大鼠胰岛细胞增殖、凋亡及功能影响的研究[D].广州:南方医科大学:内分泌与代谢病学,2012.